Omega-3: food sources versus supplements

For a healthy adult, the evidence favors eating fish over taking fish oil capsules. The largest trials of store-strength omega-3 supplements, about 1 gram a day, found no reduction in heart attacks, strokes, cardiovascular deaths, or cancer compared with placebo. Observational studies consistently link one to two servings of fish a week with lower rates of coronary heart disease and sudden cardiac death, and heart organizations base their advice on that pattern rather than on supplements (Rimm et al., 2018).

There are two exceptions. People who eat no fish get very little EPA and DHA from the rest of their diet, and a supplement is the only practical way to raise their intake. And one large trial of a high-dose prescription form of purified EPA, in people with heart disease or diabetes and high triglycerides, did reduce cardiovascular events, though a similar trial with a different formulation did not.

This article is for adults wondering whether to buy fish oil, and for people who do not eat fish.

What omega-3 fats are and where they come from

Alpha-linolenic acid, or ALA, is the omega-3 in plant foods such as flaxseed, chia seeds, walnuts, and canola oil. EPA and DHA, the long-chain forms, come almost entirely from fish, shellfish, and algae. The body converts ALA into EPA and DHA at reported rates below 15 percent, so eating flaxseed is not equivalent to eating salmon. The official intake level for adults applies only to ALA: 1.6 grams a day for men and 1.1 grams for women. There is no official recommended amount of EPA and DHA (National Institutes of Health, Office of Dietary Supplements).

A 3-ounce serving of cooked Atlantic salmon provides about 1.6 to 1.8 grams of EPA plus DHA, herring about 1.7 grams, canned sardines about 1.2 grams, and canned light tuna about 0.2 grams. A standard 1,000-milligram fish oil capsule contains about 300 milligrams of EPA plus DHA. American adults average only about 90 milligrams a day from food (National Institutes of Health, Office of Dietary Supplements).

What the supplement trials found

The best single test of ordinary fish oil in healthy people is the VITAL trial, which randomly assigned 25,871 American adults, men 50 and older and women 55 and older without heart disease or cancer, to 1 gram a day of fish oil or placebo for a median of 5.3 years. Major cardiovascular events occurred in 386 people taking fish oil and 419 taking placebo, a difference that was not statistically significant, and cancer rates were the same. A secondary analysis found fewer heart attacks in the fish oil group, with a hazard ratio of 0.72, but a secondary outcome in a trial whose primary result was null is suggestive, not conclusive (Manson et al., 2019).

A Cochrane review pooled 86 randomized trials with 162,796 participants, most of them testing fish oil capsules for a year or more. It found high-certainty evidence that long-chain omega-3 supplements have little or no effect on death from any cause, with a risk ratio of 0.97, or on cardiovascular events overall. There was low-certainty evidence of a small reduction in coronary heart disease events, with 167 people needing to take supplements to prevent one. Supplements did reliably lower triglycerides by about 15 percent. Increasing plant-based ALA had little or no effect on mortality or heart disease (Abdelhamid et al., 2020).

The high-dose prescription trials

Two large trials tested 4 grams a day in people on statins who had heart disease or diabetes and elevated triglycerides. The first, using a highly purified EPA, enrolled 8,179 patients for a median of 4.9 years. The main composite of cardiovascular events occurred in 17.2 percent of the EPA group and 22.0 percent of the placebo group, a 25 percent relative reduction, and cardiovascular death was also lower. The trial was funded by the drug's manufacturer (Bhatt et al., 2019).

The second trial gave a 4-gram combination of EPA and DHA or corn oil to 13,078 similar patients. It was stopped early for a low probability of benefit; the primary outcome occurred in 12.0 percent of the omega-3 group and 12.2 percent of the corn oil group (Nicholls et al., 2020). Why the two trials disagree is still debated. For a general reader, the point is that neither tested the capsules sold in stores, and both enrolled high-risk patients under medical supervision. Anyone with high triglycerides or heart disease should ask their doctor about prescription omega-3 rather than self-prescribing a high dose.

What eating fish is linked to

Trials of fish itself are scarce, because it is hard to randomize people to eat fish for years, and the Cochrane reviewers noted little evidence from the few that tried. The case for fish rests mainly on observational cohorts, which have repeatedly found lower rates of coronary heart disease, heart failure, ischemic stroke, and sudden cardiac death among regular fish eaters. After reviewing this evidence, the American Heart Association advised one to two seafood meals a week, noting that the benefit is clearest when seafood replaces less healthy foods (Rimm et al., 2018). Observational studies cannot prove cause, since fish eaters differ in income, smoking, and other habits, but the association has held up across many populations.

The U.S. Dietary Guidelines recommend at least 8 ounces of seafood a week for a 2,000-calorie diet, or two servings of about 4 ounces (U.S. Food and Drug Administration). Two servings of salmon, sardines, herring, or mackerel would supply roughly 2 to 3.5 grams of EPA plus DHA a week.

Risks and side effects

The most important recent finding is a link between omega-3 supplements and atrial fibrillation, an irregular heart rhythm that raises stroke risk. A meta-analysis of 7 large trials with 81,210 participants found that people assigned to omega-3 supplements were 25 percent more likely to develop atrial fibrillation than those on placebo. The risk was dose-related: a 12 percent increase in trials using 1 gram a day or less, and a 49 percent increase in trials using more (Gencer et al., 2021). The purified EPA trial also saw more hospitalizations for atrial fibrillation, 3.1 percent versus 2.1 percent (Bhatt et al., 2019).

Otherwise the safety record is reasonable. The FDA considers supplements providing up to 5 grams a day of EPA plus DHA safe when used as directed; doses of 2 to 15 grams a day can lengthen bleeding time, so people on blood thinners should tell their doctor. Digestive upset is the common complaint: in the 4-gram EPA-plus-DHA trial, it occurred in 24.7 percent of people on omega-3 versus 14.7 percent on corn oil (Nicholls et al., 2020). With fish, the concern is mercury. The FDA and EPA list salmon, sardines, trout, anchovies, and canned light tuna among the lowest-mercury choices, and advise pregnant and breastfeeding women and young children to avoid king mackerel, swordfish, shark, marlin, orange roughy, and bigeye tuna (U.S. Food and Drug Administration).

A reasonable approach

• If you eat fish, aim for two servings a week, preferring oily fish such as salmon, sardines, herring, mackerel, and trout. A supplement on top of that has no demonstrated benefit for a healthy adult.
• If you eat no fish, a daily capsule or an algae-based EPA and DHA product is a reasonable way to avoid a very low intake, keeping to about 1 gram a day or less given the atrial fibrillation findings.
• If you have heart disease, high triglycerides, or a history of atrial fibrillation, talk to your doctor before starting any omega-3 supplement.
• Walnuts, flaxseed, and chia are good foods but are not a substitute for EPA and DHA because of the low conversion rate.

Sources

• Omega-3 Fatty Acids: Fact Sheet for Health Professionals (National Institutes of Health, Office of Dietary Supplements) — U.S. government reference on intake levels, food content, and safety
• Marine n-3 fatty acids and prevention of cardiovascular disease and cancer (Manson et al., New England Journal of Medicine, 2019) — randomized placebo-controlled trial, n=25,871, median 5.3 years
• Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease (Abdelhamid et al., Cochrane Database of Systematic Reviews, 2020) — systematic review and meta-analysis of 86 randomized trials, n=162,796
• Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia (Bhatt et al., New England Journal of Medicine, 2019) — randomized trial of 4 g/day purified EPA, n=8,179, industry funded
• Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH trial (Nicholls et al., JAMA, 2020) — randomized trial of 4 g/day EPA plus DHA, n=13,078, stopped early for futility
• Seafood long-chain n-3 polyunsaturated fatty acids and cardiovascular disease: a science advisory from the American Heart Association (Rimm et al., Circulation, 2018) — expert advisory reviewing observational and trial evidence on fish intake
• Effect of long-term marine omega-3 fatty acids supplementation on the risk of atrial fibrillation in randomized controlled trials of cardiovascular outcomes (Gencer et al., Circulation, 2021) — systematic review and meta-analysis of 7 trials, n=81,210
• Advice about Eating Fish (U.S. Food and Drug Administration and Environmental Protection Agency) — U.S. government guidance on seafood servings and mercury